The laboratory's objective is to isolate and chemically characterize extracellular matrix components and to study their role in differentiation and expression of malignancy. Fragments of fibronectin that interact with collagen, glycosaminoglycans or cell surfaces have been isolated and characterized with monoclonal antibodies. The domain of fibronectin that interacts with cells has been isolated as an 11 kilodalton peptic fragment. This fragment, when used to coat plastic, causes cells to attach and spread on the coated surface. The complete amino acid sequence of this fragment has been determined from the protein and from cloned cDNA. A synthetic 30-amino acid peptide based on this sequence has been shown to have the cell-attachment activity. Fragmentation studies similar to those with fibronectin are being conducted on laminin and another adhesive protein, vitronectin (serum-spreading factor). Defined extracellular matrices constructed with these proteins as well as collagen(s) and proteoglycans are being studied for their effects on the differentiation of various types of normal and malignant cells. Current studies also aim at the identification of the cell surface receptor for fibronectin. The synthetic peptides with the cell-attachment activity will be used as probes for this purpose. These studies will help understand the normal cell adhesion mechanisms and how the disturbances of these mechanisms contribute to the properties of malignant cells.